TransEBUS: The interpretation of endobronchial ultrasound image using hybrid transformer for differentiating malignant and benign mediastinal lesions.

The purpose of this study is to establish a deep learning automatic assistance diagnosis system for benign and malignant classification of mediastinal lesions in endobronchial ultrasound (EBUS) images. EBUS images are in the form of video and contain multiple imaging modes. Different imaging modes and different frames can reflect the different characteristics of lesions. Compared with previous studies, the proposed model can efficiently extract and integrate the spatiotemporal relationships between different modes and does not require manual selection of representative frames. In recent years, Vision Transformer has received much attention in the field of computer vision. Combined with convolutional neural networks, hybrid transformers can also perform well on small datasets. This study designed a novel deep learning architecture based on hybrid transformer called TransEBUS. By adding learnable parameters in the temporal dimension, TransEBUS was able to extract spatiotemporal features from insufficient data. In addition, we designed a two-stream module to integrate information from three different imaging modes of EBUS. Furthermore, we applied contrastive learning when training TransEBUS, enabling it to learn discriminative representation of benign and malignant mediastinal lesions. The results show that TransEBUS achieved a diagnostic accuracy of 82% and an area under the curve of 0.8812 in the test dataset, outperforming other methods. It also shows that several models can improve performance by incorporating two-stream module. Our proposed system has shown its potential to help physicians distinguishing benign and malignant mediastinal lesions, thereby ensuring the accuracy of EBUS examination.

Intertwined Biosynthesis of Skyrin and Rugulosin A Underlies the Formation of Cage-Structured Bisanthraquinones.

Skyrin and rugulosin A are bioactive bisanthraquinones found in many fungi, with the former suggested as a precursor of hypericin (a diversely bioactive phytochemical) and the latter characterized by its distinct cage-like structure. However, their biosynthetic pathways remain mysterious, although they have been characterized for over six decades. Here, we present the rug gene cluster that governs simultaneously the biosynthesis of skyrin and rugulosin A in Talaromyces sp. YE3016, a fungal endophyte residing in Aconitum carmichaeli. A combination of genome sequencing, gene inactivation, heterologous expression, and biotransformation tests allowed the identification of the gene function, biosynthetic precursor, and enzymatic sets involved in their molecular architecture constructions. In particular, skyrin was demonstrated to form from the 5,5'-dimerization of emodin radicals catalyzed by RugG, a cytochrome P450 monooxygenase evidenced to be potentially applicable for the (chemo)enzymatic synthesis of dimeric polyphenols. The fungal aldo-keto reductase RugH was shown to be capable of hijacking the closest skyrin precursor (CSP) immediately after the emodin radical coupling, catalyzing the ketone reduction of CSP to inactivate its tautomerization into skyrin and thus allowing for the spontaneous intramolecular Michael addition to cyclize the ketone-reduced form of CSP into rugulosin A, a representative of diverse cage-structured bisanthraquinones. Collectively, the work updates our understanding of bisanthraquinone biosynthesis and paves the way for synthetic biology accesses to skyrin, rugulosin A, and their siblings.

Naturally Occurring Flavonoids and Isoflavonoids and Their Microbial Transformation: A Review.

Flavonoids and isoflavonoids are polyphenolic secondary metabolites usually produced by plants adapting to changing ecological environments over a long period of time. Therefore, their biosynthesis pathways are considered as the most distinctive natural product pathway in plants. Seemingly, the flavonoids and isoflavones from fungi and actinomycetes have been relatively overlooked. In this review, we summarized and classified the isoflavones and flavonoids derived from fungi and actinomycetes and described their biological activities. Increasing attention has been paid to bioactive substances derived from microorganism whole-cell biotransformation. Additionally, we described the utilization of isoflavones and flavonoids as substrates by fungi and actinomycetes for biotransformation through hydroxylation, methylation, halogenation, glycosylation, dehydrogenation, cyclisation, and hydrogenation reactions to obtain rare and highly active biofunctional derivatives. Overall, among all microorganisms, actinomycetes are the main producers of flavonoids. In our review, we also summarized the functional genes involved in flavonoid biosynthesis.

Self-Reference Analysis Based on Temperature Difference Absorption Spectra.

The direct qualitative identification of pure liquids in laboratories and in security checks is generally performed by the detection of the refractive index or the permittivity. However, refractive indices are strongly influenced by temperature, while the permittivities of some organics are difficult to differentiate. On the other hand, the quantitative monitoring of samples with high concentration in plating baths and in chemical production lines are generally performed via a "Sampling-Dilution-Analysis" approach because of significant deviations from the linear range at high concentration, which makes the real-time monitoring of concentrated samples difficult. Here, we propose a self-reference analysis (SRA) method to directly analyze pure liquids and concentrated samples based on temperature difference absorption spectra (TDAS) without the need for dilution. This method was performed by simultaneously scanning the spectra of the reference and the sample, which are both obtained from the same analyte for detection but are at different temperatures. Compared to conventional absorption spectra with a blank reference, the red-shifted peak wavelengths of TDAS enable the detection of many far UV absorptive compounds in the near-ultraviolet region (λ > 190 nm). More importantly, organic compounds with similar structures can be easily distinguished. In addition, TDAS can also be used for the quantitative detection of concentrated analytes. The proposed SRA-TDAS method is a rapid and effective method; this approach does not require dilution and utilizes a self-reference, implying the wide potential applicability in security checks, and the real-time monitoring of concentrated compounds in chemical production lines.

Tunable size selectivity and nanoparticle immobilization on a photonic crystal optical trap.

We harness residual thermal effects in a low-absorptivity system to manipulate parallel optical trapping of particles on the nanoscale. A photonic crystal is used to generate a 2D array of optical traps. We show that the size selectivity of the trap can be tuned by adding a non-ionic surfactant to the solution, altering the thermophoretic effect that delivers nanoparticles to trapping sites. We further show that particles can be permanently immobilized on the photonic crystal via photopolymerization of the trapping medium.

The bioenergetics mechanisms and applications of sulfate-reducing bacteria in remediation of pollutants in drainage: A review.

Sulfate-reducing bacteria (SRB), a group of anaerobic prokaryotes, can use sulfur species as a terminal electron acceptor for the oxidation of organic compounds. They not only have significant ecological functions, but also play an important role in bioremediation of contaminated sites. Although numerous studies on metabolism and applications of SRB have been conducted, they still remain incompletely understood and even controversial. Fully understanding the metabolism of SRB paves the way for allowing the microorganisms to provide more beneficial services in bioremediation. Here we review progress in bioenergetics mechanisms and application of SRB including: (1) electron acceptors and donors for SRB; (2) pathway for sulfate reduction; (3) electron transfer in sulfate reduction; (4) application of SRB for economical and concomitant treatment of heavy metal, organic contaminants and sulfates. Moreover, current knowledge gaps and further research needs are identified.

Molar Range Detection Based on Sideband Differential Absorption Spectroscopy with a Concentrated Reference.

Conventional absorption spectroscopy (CAS) with a blank reference has only a slight capacity to detect high concentrations at characteristic wavelengths owing to the corresponding large molar absorption coefficient (ε) on the scale of 103 or 104 cm-1 M-1. To monitor concentrated analytes as high as the molar range in a plating bath and on a chemical production line, we propose a new approach using sideband differential absorption spectroscopy (SDAS). SDAS is obtained by subtracting the absorption spectra of the samples, A(λ,Cx), from that of a reference containing a concentrated standard analyte, A(λ,Cref>Cx), resulting in concave spectra with peaks at the sideband of conventional spectra with generally low ε values on the scale of 100 cm-1 M-1 or less. The negative absorbance changes linearly with the sample concentration at a certain peak wavelength, obeying Lambert-Beer's law. In this work, SDAS was obtained and verified using inorganic and organic substances, such as chromate potassium, rhodamine B, and paracetamol.

Near-Field, On-Chip Optical Brownian Ratchets.

Nanoparticles in aqueous solution are subject to collisions with solvent molecules, resulting in random, Brownian motion. By breaking the spatiotemporal symmetry of the system, the motion can be rectified. In nature, Brownian ratchets leverage thermal fluctuations to provide directional motion of proteins and enzymes. In man-made systems, Brownian ratchets have been used for nanoparticle sorting and manipulation. Implementations based on optical traps provide a high degree of tunability along with precise spatiotemporal control. Here, we demonstrate an optical Brownian ratchet based on the near-field traps of an asymmetrically patterned photonic crystal. The system yields over 25 times greater trap stiffness than conventional optical tweezers. Our technique opens up new possibilities for particle manipulation in a microfluidic, lab-on-chip environment.

Enhanced and selective optical trapping in a slot-graphite photonic crystal.

Applicability of optical trapping tools for nanomanipulation is limited by the available laser power and trap efficiency. We utilized the strong confinement of light in a slot-graphite photonic crystal to develop high-efficiency parallel trapping over a large area. The stiffness is 35 times higher than our previously demonstrated on-chip, near field traps. We demonstrate the ability to trap both dielectric and metallic particles of sub-micron size. We find that the growth kinetics of nanoparticle arrays on the slot-graphite template depends on particle size. This difference is exploited to selectively trap one type of particle out of a binary colloidal mixture, creating an efficient optical sieve. This technique has rich potential for analysis, diagnostics, and enrichment and sorting of microscopic entities.

The dynamics of giant unilamellar vesicle oxidation probed by morphological transitions.

We have studied the dynamics of Lissamine Rhodamine B dye sensitization-induced oxidation of 1,2-dioleoyl-sn-glycero-3-phosphocholine (DOPC) giant unilamellar vesicles (GUVs), where the progression of the underlying chemical processes was followed via vesicle membrane area changes. The surface-area-to-volume ratio of our spherical GUVs increased after as little as ten seconds of irradiation. The membrane area expansion was coupled with high amplitude fluctuations not typical of GUVs in isoosmotic conditions. To accurately measure the area of deformed and fluctuating membranes, we utilized a dual-beam optical trap (DBOT) to stretch GUV membranes into a geometrically regular shape. Further oxidation led to vesicle contraction, and the GUVs became tense, with micron-scale pores forming in the bilayer. We analyzed the GUV morphological behaviors as two consecutive rate-limiting steps. We also considered the effects of altering DOPC and 1,2-dipalmitoyl-sn-glycero-3-phosphoethanolamine-N-(lissamine rhodamine B sulfonyl) (RhDPPE) concentrations. The resulting kinetic model allows us to measure how lipid molecular area changes during oxidation, as well as to determine the rate constants controlling how quickly oxidation products are formed. Controlled membrane oxidation leading to permeabilization is also a potential tool for drug delivery based on engineered photosensitizer-containing lipid vesicles.

Solar heating of GaAs nanowire solar cells.

We use a coupled thermal-optical approach to model the operating temperature rise in GaAs nanowire solar cells. We find that despite more highly concentrated light absorption and lower thermal conductivity, the overall temperature rise in a nanowire structure is no higher than in a planar structure. Moreover, coating the nanowires with a transparent polymer can increase the radiative cooling power by 2.2 times, lowering the operating temperature by nearly 7 K.

Viscoelastic deformation of lipid bilayer vesicles.

Lipid bilayers form the boundaries of the cell and its organelles. Many physiological processes, such as cell movement and division, involve bending and folding of the bilayer at high curvatures. Currently, bending of the bilayer is treated as an elastic deformation, such that its stress-strain response is independent of the rate at which bending strain is applied. We present here the first direct measurement of viscoelastic response in a lipid bilayer vesicle. We used a dual-beam optical trap (DBOT) to stretch 1-palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC) giant unilamellar vesicles (GUVs). Upon application of a step optical force, the vesicle membrane deforms in two regimes: a fast, instantaneous area increase, followed by a much slower stretching to an eventual plateau deformation. From measurements of dozens of GUVs, the average time constant of the slower stretching response was 0.225 ± 0.033 s (standard deviation, SD). Increasing the fluid viscosity did not affect the observed time constant. We performed a set of experiments to rule out heating by laser absorption as a cause of the transient behavior. Thus, we demonstrate here that the bending deformation of lipid bilayer membranes should be treated as viscoelastic.

Five New Guaiane Sesquiterpenes from the Endophytic Fungus Xylaria sp. YM 311647 of Azadirachta indica.

Five new guaiane sesquiterpenes, 1-5, were isolated from the culture broth of the endophytic fungus Xylaria sp. YM 311647, isolated from Azadirachta indica A. Juss. The structures of these compounds were elucidated on the basis of spectroscopic analyses, and their inhibitory activities against five pathogenic fungi were evaluated. All guaiane sesquiterpenes showed moderate or weak antifungal activities in a broth microdilution assay.

Two new butenolides produced by an Actinomycete Streptomyces sp.

Two new butenolides, (4S)-4,10-dihydroxydodec-2-en-1,4-olide (1) and (4S)-4,8,10-trihydroxy-10-methyldodec-2-en-1,4-olide (2), together with three known compounds, MKN-003B (3), MKN-003C (4), and cyclo(Ala-Leu) (5), were isolated from the culture broth of a bacterium of the genus Streptomyces derived from soil environment. The structures of these compounds were elucidated on the basis of spectroscopic analysis. The inhibitory activities of the butenolides against eight pathogenic fungi were evaluated. All of the butenolides showed moderate-or-weak antifungal activities in a broth microdilution assay.

Four new polyketides from an endophytic fungus Talaromyces muroii.

In our continuous work on the isolation of endophytes, the endophytic fungal strain YIMF00209 was obtained from the roots of Gmelina arborea, which is an ethnic medicinal plant mainly distributed in Southeast Asia. The fermentation extracts of the strain exhibited significant antimicrobial activities against Staphylococcus aureus, Fusarium solani, and Escherichia coli. Based on morphological characteristics and phylogenetic analysis, it was identified as Talaromyces muroii. Four new polyketides, talaromurolides A-D (1-4), along with 26 known compounds (5-30), were isolated from the culture broth of the strain in two different media. Their structures were identified based on HRESIMS, NMR, and CD spectral data. Among them, compounds 2, 4-6, 19, 22, 24, 27, 28, and 30 were isolated from the fermentation broth in CYM medium; compounds 1, 3, 7-18, 20, 21, 23, 25, 26, and 29 were obtained from the fermentation broth in PDB medium; and compounds 2, 5, and 30 were existed in both two media. Compounds 6-9, 12, 16, 20, 21, 23, 25, and 29 were obtained from the genus Talaromyces for the first time. The antimicrobial activities of several compounds were assayed against six pathogens. Compound 1 exhibited inhibitory activities against S. aureus, E. coli, Candida albicans, Salmonella typhimurium, and Botrytis cinerea with MIC value of 64 µg/mL. Compound 25 exhibited antibacterial activity against E. coli with MIC value of 32 µg/mL.

3-O-Methyl-D-Glucose Blunts Cold Ischemia Damage in Kidney via Inhibiting Ferroptosis.

BACKGROUND: The glucose derivative 3-O-methyl-D-glucose (OMG) is used as a cryoprotectant in freezing cells. However, its protective role and the related mechanism in static cold storage (CS) of organs are unknown. The present study aimed to investigate the effect of OMG on cod ischemia damage in cold preservation of donor kidney. METHODS: Pretreatment of OMG on kidney was performed in an isolated renal cold storage model in rats. LDH activity in renal efflux was used to evaluate the cellular damage. Indicators including iron levels, mitochondrial damage, MDA level, and cellular apoptosis were measured. Kidney quality was assessed via a kidney transplantation (KTx) model in rats. The grafted animals were followed up for 7 days. Ischemia reperfusion (I/R) injury and inflammatory response were assessed by biochemical and histological analyses. RESULTS: OMG pretreatment alleviated prolonged CS-induced renal damage as evidenced by reduced LDH activities and tubular apoptosis. Kidney with pCS has significantly increased iron, MDA, and TUNEL+ cells, implying the increased ferroptosis, which has been partly inhibited by OMG. OMG pretreatment has improved the renal function (p <0.05) and prolonged the 7-day survival of the grafting recipients after KTx, as compared to the control group. OMG has significantly decreased inflammation and tubular damage after KTx, as evidenced by CD3-positive cells and TUNEL-positive cells. CONCLUSION: Our study demonstrated that OMG protected kidney against the prolonged cold ischemia-caused injuries through inhibiting ferroptosis. Our results suggested that OMG might have potential clinical application in cold preservation of donor kidney.

Enantioselective copper-catalyzed azidation/click cascade reaction for access to chiral 1,2,3-triazoles.

Chiral 1,2,3-triazoles are highly attractive motifs in various fields. However, achieving catalytic asymmetric click reactions of azides and alkynes for chiral triazole synthesis remains a significant challenge, mainly due to the limited catalytic systems and substrate scope. Herein, we report an enantioselective azidation/click cascade reaction of N-propargyl-ß-ketoamides with a readily available and potent azido transfer reagent via copper catalysis, which affords a variety of chiral 1,2,3-triazoles with up to 99% yield and 95% ee under mild conditions. Notably, chiral 1,5-disubstituted triazoles that have not been accessed by previous asymmetric click reactions are also prepared with good functional group tolerance.

Two new steroids from an endophytic fungus Phomopsis sp.

Two new steroids, (14ß,22E)-9,14-dihydroxyergosta-4,7,22-triene-3,6-dione (1) and (5α,6ß,15ß,22E)-6-ethoxy-5,15-dihydroxyergosta-7,22-dien-3-one (2), together with three known steroids, calvasterols A and B (3 and 4, resp.), and ganodermaside D (5), were isolated from the culture broth of an endophytic fungus Phomopsis sp. isolated from Aconitum carmichaeli. The structures of these compounds were elucidated on the basis of spectroscopic analysis, and their inhibitory activities against six pathogenic fungi were evaluated. Most of the compounds showed moderate or weak antifungal activities in a broth-microdilution assay.

Heating promoted super sensitive electrochemical detection of p53 gene based on alkaline phosphatase and nicking endonuclease Nt.BstNBI-assisted target recycling amplification strategy at heated gold disk electrode.

An ultrasensitive electrochemical biosensor for detecting p53 gene was fabricated based on heated gold disk electrode coupling with endonuclease Nt.BstNBI-assisted target recycle amplification and alkaline phosphatase (ALP)-based electrocatalytic signal amplification. For biosensor assembling, biotinylated ssDNA capture probes were first immobilized on heated Au disk electrode (HAuDE), then combined with streptavidin-alkaline phosphatase (SA-ALP) by biotin-SA interaction. ALP could catalyze the hydrolysis of ascorbic acid 2-phosphate (AAP) to produce ascorbic acid (AA). While AA could induce the redox cycling to generate electrocatalytic oxidation current in the presence of ferrocene methanol (FcM). When capture probes hybridized with p53, Nt.BstNBI would recognize and cleave the duplexes and p53 was released for recycling. Meanwhile, the biotin group dropt from the electrode surface and subsequently SA-ALP could not adhere to the electrode. The signal difference before and after cleavage was proportional to the p53 gene concentration. Furthermore, with electrode temperature elevated, the Nt.BstNBI and ALP activities could be increased, greatly improving the sensitivity and efficiency for p53 detection. A detection limit of 9.5 × 10-17 M could be obtained (S/N = 3) with an electrode temperature of 40 °C, ca. four magnitudes lower than that at 25 °C.

[Distribution Characteristics, Ecological Risks, and Source Identification of Heavy Metals in Cultivated Land Under Non-grain Production].

The purpose of this study was to explore the distribution characteristics and potential ecological risks of soil heavy metal pollution of cultivated land under non-grain production. Taking a typical area around Hangzhou Bay as an example, 254 topsoil samples (0-20 cm) of cultivated land were collected, and the content of eight soil heavy metals in four different cultivated land use types, including grain, seedlings, vegetables, and fruits, was analyzed. The ecological risk was assessed by the Nemerow pollution index and the potential ecological risk index, and the PMF model was used to identify the source of soil heavy metals in the study area. The results showed that the average contents of As, Cr, Cd, Cu, Hg, Ni, and Zn were all higher than the soil background value, except for Pb, but were lower than the national risk control standard for soil contamination of agricultural land. Non-grain production had a significant impact on the accumulation of heavy metals in soil. The content of heavy metals in nurseries and orchards was relatively high, followed by vegetable fields, and the lowest in grain fields. The Nemerow index showed that the cultivated land in the study area was in a light pollution level as a whole, and the single-factor pollution risks of Hg, Cd, and As were relatively high. The potential ecological risk levels of heavy metals in different cultivated land use types were:nurseries>orchards>vegetable fields>grain fields. The PMF results showed that the main sources of soil heavy metals in the study area were mixed sources of industrial emissions (36.8%), natural parent material sources (28.4%), atmospheric deposition sources (21.4%), and agricultural activity sources (13.4%). In conclusion, the increase in the application of chemical fertilizers and pesticides was the direct reason for the increase in soil heavy metal content caused by non-grain production of the cultivated land, whereas the industrial and mining emissions and atmospheric deposition accelerated the increase in soil heavy metal content in the study area.